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Diabetic nephropathy is a tragic illness. Its often insidious onset
in the insulin dependent (type I) diabetic, typically a young
adult, heralds the last act in the course of a disease that will
increasingly become the dominant preoccupation in the patient's
shortened life. For most type II diabetics, the beginning of
clinical renal insufficiency is but a phase in a continuous
deterioration that affects the integrity ofjob, marriage, and
family. The nephropathic diabetic is hypertensive, has worsening
retinopathy, and more often than not, is also plagued by peripheral
vascular insufficiency, heart disease, gastrointestinal
malfunction, and deepening depression. Until the 1980's, few type I
diabetics who became uremic (because ofdiabetic nephropathy) lived
for more than two years. Hardly any attained true rehabilitation.
This dismal prognosis is changing substantially for the better.
Research in diabetes has resulted in striking advances at both ends
of the type I diabetic's natural history. In one exciting clinical
trial now underway in London, Ontario, halfofchildhood diabetics
treated with cyclosporine within six weeks of onset
evince"permanent" disappearanceofhyperglycemia and the need for
insulin. At the otherendofthe natural historyofdiabetes for the
nephropathic patientwith worsening eye disease (renal-retinal
syndrome), who receives a kidney transplant, patient and graft
survival, two years after cadaveric kidney transplantation in type
I diabetics is now equal to that of the nondiabetic."
The breadth of research efforts represented by the many excellent
papers in these proceedings is an eloquent testimonial to the idea
of one man Dr. Josiah Brown-to whose memory this volume is
dedicated. His tragic and unexpected loss in a swimming accident in
August 1985 brought to an abrupt close a long and distinguished
career as a physician and scientist. The possibility of using fetal
pancreas tissue for transplantation into insulin-deficient diabetic
recipients had intrigued Dr. Brown for several years prior to 1972,
when he began in earnest to assemble a research team to explore
this idea in detail. He felt that improvements in the formulation
and administration of insulin (even the later recombinant human
insulin) had taken us about as far as we could go in treating
diabetes, and that methods for achieving complete cures must be
explored. Numerous advantages of the fetal pancreas quickly became
apparent, and were explored scientifically by Dr. Brown and his
group. Transplanted pancreas tissue from a fetal donor of the
appropriate developmental stage engrafts quickly, and can reverse
diabetes very efficiently (1-3). By shunting the venous'drainage of
the graft into the hepatic portal vein, a single pancreatic
rudiment can, in time, provide enough insulin to restore
normoglycemia and urine volume in a diabetic adult recipient (4).
As with fetal pancreas rudiments in culture, transplanted fetal
pancreas tissue loses its exocrine character, while continuing to
develop and maintain endocrine function.
Protocols for Enhancing Function of Fetal Islets in vitro and
following Transplantation (A. Hayek, G.M. Beattie). Expression of
Two Nonallelic Reg Genes in the Developing Human Pancreas: Effects
in vitro of Nicotinamide and Maternal Growth Factors (B. Formby et
al.). Preparation of Fetal Islets for Transplantation: Importance
of Growth Factors (D.A. Hullet et al.). Studies of Fetal Porcine
Isletlike Cell Clusters-A Tissue Source for Xenotransplantation in
Insulindependent Diabetes Mellitus? (S. Sandler). Basic Biology of
Pig Fetal Pancreas and Its Use as an Allograft (B.E. Tuch et al.).
Combined Transplantation of Adult and Fetal Islets for Improvement
of Graft Function (Y. Mullen). Studies on Pretreatment of Human
Fetal Islet in Vitro and Clinical Islet Transplantation in China
(Y.F. Hu et al.). The Use of Human Fetal Islet Tissue for
Adjunctive Treatment in Insulindependent Diabetic Patients: The
Case for 'Partial Success' (L. JovanovicPeterson et al.). Longterm
Studies with Cultured and Cryopreserved Human Fetal Islets for
Islet Transplantation in Hungary (G. Farkas). Fetal Islet
Transplantation and Pregnancy (C.M. Peterson et al.). Encapsulated
Human Islet Transplant Trials in Type I Diabetic Patients (P.
SoonShiong). 4 additional articles. Index.
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